Expert Review of Clinical Pharmacology最新文献

Introduction: Vitiligo is a chronic autoimmune skin disorder characterized by progressive melanocyte loss, resulting in well-demarcated depigmented patches that significantly impact quality of life. Affecting 0.5-2% of the global population, vitiligo poses both psychosocial and therapeutic challenges. Despite multiple conventional therapies such as corticosteroids, calcineurin inhibitors, and phototherapy, durable repigmentation remains difficult to achieve.

Areas covered: This review summarizes recent advances in understanding the emerging medical treatment of vitiligo. A targeted literature search was conducted using PubMed, Embase, and ClinicalTrials.gov from inception to April 2025. Key clinical trial data are discussed to evaluate efficacy, safety and durability of response across therapeutic classes.

Expert opinion: The approval of topical ruxolitinib marks a pivotal step toward precision therapy in vitiligo. Ongoing studies of combination and maintenance regimens offer promise for sustained repigmentation and disease stabilization. However, optimizing long-term outcomes requires continued translational research to elucidate mechanisms of relapse, improve accessibility of emerging therapies and personalize treatment strategies to individual disease phenotypes.

Background: Doxycycline post-exposure prophylaxis is recommended for men who have sex with men at high risk for sexually transmitted infections. Accurate doxycycline measures ensure consistent evaluation of adherence and efficacy.

Research design and methods: Participants received 200 mg doxycycline (blood collected in citrate [n = 20] or heparin [n = 14] tubes). Ex vivo analyses compared exogenous doxycycline spiked into blood from matched donors collected in citrate and heparin (n = 8) or EDTA and heparin (n = 9). Plasma doxycycline was quantified with liquid chromatography-tandem mass spectrometry and reported as geometric mean [95% CI].

Results: After dosing, plasma doxycycline AUC_24-72 h from citrate blood (17.07 µg/mL*hr [13.89-20.99]) was 3-times lower than heparin blood (54.57 [44.18-67.40]). Similarly, reduced plasma doxycycline was observed when drug was spiked into citrate (0.062 µg/mL [0.059-0.065]) versus heparin blood (0.084 µg/mL [0.077-0.092]) from matched donors (p = 0.0002). EDTA blood, also showed significantly lower plasma doxycycline (0.052 µg/mL [0.049-0.054]) than heparin blood (0.078 µg/mL [0.071-0.084]) (p < 0.0001).

Conclusions: Chelating anticoagulants significantly reduce plasma doxycycline concentrations, likely through disruption of doxycycline-metal ion complexes and increased drug partitioning in red blood cells. Pharmacologically focused doxycycline research should prioritize blood collection in non-chelating anticoagulants or apply a correction factor if chelating anticoagulants are used.

Clinical trial registration: NCT04860505, NCT05853120, and NCT06545656.

Introduction: Traditional therapeutic drug monitoring (TDM) faces limitations in accuracy and adaptability, often failing to optimize therapy for complex patients. Machine learning (ML) is emerging as a powerful tool to overcome these challenges, offering a data-driven paradigm to enhance therapeutic outcomes and minimize toxicity for drugs with narrow therapeutic indices.

Areas covered: This review synthesizes the evolution of ML in TDM. We cover foundational models that predict drug exposure from sparse data using either real-world or simulation-based training. We then explore the extension of these techniques to proactive first-dose optimization and the recent development of hybrid models, which integrate the physiological interpretability of population pharmacokinetic frameworks with the corrective power of ML.

Expert opinion: The future of TDM lies not in replacing mechanistic models, but in their convergence with ML. While promising, clinical translation requires overcoming critical barriers in data access, model interpretability, and workflow integration. The long-term trajectory points toward dynamic Digital Twins capable of forecasting patient-specific benefit-risk profiles. Ultimately, validated hybrid tools embedded in clinical decision support systems could establish proactive, individualized dosing as the new standard of care in personalized pharmacotherapy.

Objective: This study aimed to identify risk factors associated with mitral annular calcification (MAC) in patients with hypertrophic obstructive cardiomyopathy (HOCM) and to evaluate its relationship with clinical outcomes.

Methods: A total of 310 patients with HOCM who underwent interventricular septal myectomy were retrospectively analyzed. Patients were divided into a MAC group (n = 24) and a non-MAC group (n = 286). Demographic characteristics, echocardiographic parameters, and clinical data were compared between groups. Major adverse cardiovascular and cerebrovascular event (MACCE) and circulating levels of brain natriuretic peptide, Apelin, and Galectin-3 were analyzed.

Results: Patients with MAC were older and showed higher prevalence of aortic annular calcification, mitral leaflet thickening, and moderate-to-severe tricuspid regurgitation (P < 0.05). Multivariate analysis identified gender, age, aortic annular calcification, moderate-to-severe tricuspid regurgitation, and mitral leaflet thickening as independent risk factors for MAC. Patients with MAC showed larger left ventricular end-diastolic volume, reduced left ventricular ejection fraction, and greater left atrium mass, and a higher incidence of MACCE than those without MAC (P < 0.05).

Conclusion: In HOCM undergoing septal myectomy, MAC is associated with adverse cardiac remodeling and unfavorable clinical outcomes. Identification of related factors may aid risk stratification and perioperative management.

Introduction: Non - clear cell renal cell carcinoma (nccRCC) encompasses a heterogeneous group of rare malignancies, representing approximately 20-25% of all renal cancers. Unlike clear cell RCC (ccRCC), these subtypes - papillary, chromophobe, collecting duct, translocation, molecularly defined variants and others - display distinct biological behaviors, genetic profiles, and therapeutic sensitivities, which preclude a uniform treatment approach.

Areas covered: This review provides an updated overview of systemic therapy for nccRCC, integrating evidence from prospective trials, retrospective series, and translational research. For most of these histologies, immune checkpoint inhibitor (ICI) - based combinations (e.g. pembrolizumab - lenvatinib, nivolumab - cabozantinib or nivolumab-ipilimumab) have demonstrated the best activity. In chromophobe RCC (chRCC), also mechanistic target of rapamycin (mTOR) inhibition appears particularly relevant, whereas in collecting duct carcinoma and renal medullary carcinoma platinum-based chemotherapy continue to have an important role, with cabozantinib showing encouraging results. Novel biomarker-driven approaches are emerging for selected molecular subsets.

Expert opinion: Although remarkable progress has been achieved, the optimal therapeutic strategy for nccRCC remains undefined. Future efforts should focus on histology- and biomarker-driven clinical trials, molecular stratification, to optimize efficacy across subtypes. International collaboration is crucial to overcome the challenges posed by the rarity and biological heterogeneity of these tumors.

Introduction: In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), long-term dual antiplatelet therapy (DAPT) is the current standard of care. However, recent evidence suggests that shortening DAPT duration in favor of single antiplatelet therapy (SAPT) can optimize the overall clinical benefit, as it can prevent bleeding without significant tradeoff in ischemic events.

Areas covered: In this narrative review, we synthesize current evidence from PubMed and SCOPUS on SAPT vs DAPT regimens in CAD patients undergoing PCI, including pharmacodynamic and clinical outcomes data, and we propose an algorithm for appropriate antiplatelet regimen selection depending on the ischemic and bleeding risk profile of the individual patient.

Expert opinion: The landscape of antiplatelet treatment regimens has significantly evolved over time, with the current trend being toward a tailored approach based on risk profile, aiming to reduce the risk of bleeding while maintaining ischemic protection. The accurate evaluation of each patient's ischemic and bleeding risk profile is of utmost importance. Dedicated tools have been developed to optimize patient risk profiling and help guide the selection of the antiplatelet regimen. Based on risk estimation, several strategies can be used to reduce the overall risk, including the selection and duration of the antiplatelet regimen.

Introduction: Little is known about the pharmacokinetics (PK) and pharmacodynamics (PD) of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) when vaped in liquid formulations. As the prevalence of vaping Δ⁹-THC in liquid forms grows, understanding the factors that influence PK/PD profiles is critical to guide future research and cannabis regulation.

Areas covered: Currently, no human studies have elucidated the PK/PD profile of Δ⁹-THC from vaped liquids, as confirmed by searches of PubMed and Embase. Using existing research on smoked cannabis and nicotine-containing e-cigarettes, this review examines the potential influence of product potency, vaporization efficiency, consumer use behaviors, aerosol bioavailability, and other constituents on the PK/PD profile of Δ⁹-THC vaped in liquid forms. Further, we hypothesize whether PK/PD of Δ⁹-THC in liquid forms may differ from smoked cannabis and address potential regulatory implications (United States-focused) of novel vaping products.

Expert opinion: While more potent than smoked cannabis, vaped liquid formulations with Δ⁹-THC may have a similar PK/PD profile through modulation of Δ⁹-THC delivery by consumer use behaviors. Potential health effects of high-potency vaping products with Δ⁹-THC in liquid form need to be carefully studied. Lastly, researchers should continue to think creatively about how this important work can progress, while restrictions on Δ⁹-THC continue to hinder research.

Background: Piperacillin population pharmacokinetic models reportedly perform poorly for critically ill females compared to males. We aimed to explore potential methods that may better adjust for female data during model development.

Research design and methods: Total piperacillin concentrations were used from a prospective observational study in NONMEM v7.5.1. Two models were developed following different approaches: classic stepwise approach and sex-specific approach. Relationship between covariates and estimated parameters were explored by statistically and graphically assessing their performance on males and females separately. Dosing regimen simulations were also performed separately by sex.

Results: A one-compartment model based on data from 70 critically ill patients (49/21 males/females) with 233 concentrations best fit the data with both approaches. Creatinine clearance was the most significant covariate for the classic approach model, while creatinine clearance was best for male patients and estimated glomerular filtration rate was best for female patients with the sex-specific approach. Dosing recommendations were different between male and female patients with the sex-specific model.

Conclusion: This study is the first to consider sex-specific covariates during the modeling process for piperacillin in critically ill patients. This approach may help reduce differences in model predictions between males and females in model-informed precision dosing strategies.

Introduction: Cumulative evidence suggests that proactive therapeutic drug monitoring (TDM) of anti-tumor necrosis factor (anti-TNF) therapy is associated with favorable outcomes in inflammatory bowel disease (IBD). However, there is limited information regarding the role of proactive TDM for de-escalating anti-TNF therapy in IBD.

Areas covered: This narrative review will provide an overview of the role of proactive TDM for anti-TNF therapy de-escalation in IBD. A literature search was performed using PubMed between 2005 and June 2025.

Expert opinion: Cumulative evidence suggests that proactive TDM plays a key role in guiding anti-TNF therapy de-escalation, as in patients with supra-therapeutic drug concentrations and discontinuation of the IMM in case of combination therapy with infliximab, as in patients with high drug concentrations prior to IMM withdrawal. Moreover, preliminary data suggest that proactive TDM may also help guiding anti-TNF therapy withdrawal, as in patients with sustained remission and undetectable or low drug concentrations at the time of drug discontinuation. Finally, proactive TDM is also important for surveillance of patients after treatment de-escalation to prevent low drug concentrations and immunogenicity. However, there are still some knowledge gaps including the ideal drug concentration before treatment de-escalation and if drug clearance rather than concentration can better guide anti-TNF therapy de-escalation.